Spark sputters on haemophilia A gene therapy safety scare

Investors compare data unfavourably with BioMarin rival

Gene therapy developer Spark Therapeutics has seen around $1bn carved off its value after it emerged that two patients in its haemophilia A gene therapy trial developed immune reactions, one of which was treated in hospital.

The 28% reduction in share price came despite the biotech saying that it intends to move SPK-8011 into a phase III testing programme later this year on the back of “near elimination of bleeds and infusions across all three doses studied” in its phase I/II trial, according to chief executive Jeff Marrazzo.

While the efficacy data looked on track, attention focused on two patients in the study treated with the dose of SPK-8011 likely to start pivotal testing, who responded to treatment but did not maintain the targeted factor VIII level (12% or more) because of an immune response that blocked its effects.

Spark CEO Jeff Marrazzo

The other five patients in that highest dose group either had no immune response or a response that was “readily controlled with a course of oral steroids,” according to Marrazzo. The two who did not respond were switched to a higher oral steroid doses , but one needed infusions delivered in hospital to resolve the reaction.

“The immune response in two of these individuals got enough a head start that steroids failed to arrest declines in the factor levels as quickly as we would have liked,” said the CEO on a conference call yesterday. Haematologists will get a chance to sift through the data in full after it’ presented at the American Society of Haematology (ASH) meeting in December.

Spark’s proposed solution is to use preventative corticosteroids in all clinical trial subjects to try to prevent that happening, a strategy it maintains has been used in other gene therapy trials, including studies of its own approved eye disease therapy Luxturna.

Some analysts were less bullish about the findings, pointing out that the immune reactions will likely prevent Spark from pushing the dose of the therapy higher and – with two patients not meeting the factor threshold because of reactions – suggesting that could affect SPK-8011’s competitive profile compared to other haemophilia A gene therapies from the likes of BioMarin Pharma, Pfizer/Sangamo Biosciences and Shire.

BioMarin’s candidate BMN 270 seems to be more effective at raising factor VIII levels, but there are questions about the durability of that effect in the second year after dosing. Meanwhile, Spark says it has data showing that SPK-8011 has maintained factor VII levels above the threshold for more than a year in two patients.

“While there is more to do, I am excited about what Spark has achieved in both haemophilia A and haemophilia B and I have no doubt now the gene therapy for haemophilia will within a few short years be a reality for people with this disease,” asserted Marrazzo on the call.